title: Independent and joint effects of the MAPT and SNCA genes in Parkinson disease.
abstract: OBJECTIVE
  We studied the independent and joint effects of the genes encoding alpha-synuclein (SNCA) and microtubule-associated protein tau (MAPT) in Parkinson disease (PD) as part of a large meta-analysis of individual data from case-control studies participating in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) consortium.
  
  
  METHODS
  Participants of Caucasian ancestry were genotyped for a total of 4 SNCA (rs2583988, rs181489, rs356219, rs11931074) and 2 MAPT (rs1052553, rs242557) single nucleotide polymorphism (SNPs). Individual and joint effects of SNCA and MAPT SNPs were investigated using fixed- and random-effects logistic regression models. Interactions were studied on both a multiplicative and an additive scale, and using a case-control and case-only approach.
  
  
  RESULTS
  Fifteen GEO-PD sites contributed a total of 5,302 cases and 4,161 controls. All 4 SNCA SNPs and the MAPT H1-haplotype-defining SNP (rs1052553) displayed a highly significant marginal association with PD at the significance level adjusted for multiple comparisons. For SNCA, the strongest associations were observed for SNPs located at the 3' end of the gene. There was no evidence of statistical interaction between any of the 4 SNCA SNPs and rs1052553 or rs242557, neither on the multiplicative nor on the additive scale.
  
  
  CONCLUSIONS
  This study confirms the association between PD and both SNCA SNPs and the H1 MAPT haplotype. It shows, based on a variety of approaches, that the joint action of variants in these 2 loci is consistent with independent effects of the genes without additional interacting effects.
authors.affiliation: INSERM, U708, Neuroepidemiology, F-75013, Paris, France. alexis.elbaz@upmc.fr
authors.forename: Alexis
authors.initials: A
authors.lastname: Elbaz
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
authors.forename: Alexandra I
authors.initials: AI
authors.lastname: Soto-Ortolaza
authors.forename: Frédéric
authors.initials: F
authors.lastname: Moisan
authors.forename: Jan
authors.initials: J
authors.lastname: Aasly
authors.forename: Grazia
authors.initials: G
authors.lastname: Annesi
authors.forename: Maria
authors.initials: M
authors.lastname: Bozi
authors.forename: Laura
authors.initials: L
authors.lastname: Brighina
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Chartier-Harlin
authors.forename: Alain
authors.initials: A
authors.lastname: Destée
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrarese
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ferraris
authors.forename: J Mark
authors.initials: JM
authors.lastname: Gibson
authors.forename: Suzana
authors.initials: S
authors.lastname: Gispert
authors.forename: Georgios M
authors.initials: GM
authors.lastname: Hadjigeorgiou
authors.forename: Barbara
authors.initials: B
authors.lastname: Jasinska-Myga
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Rejko
authors.initials: R
authors.lastname: Krüger
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Lambert
authors.forename: Katja
authors.initials: K
authors.lastname: Lohmann
authors.forename: Simone
authors.initials: S
authors.lastname: van de Loo
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Loriot
authors.forename: Timothy
authors.initials: T
authors.lastname: Lynch
authors.forename: George D
authors.initials: GD
authors.lastname: Mellick
authors.forename: Eugénie
authors.initials: E
authors.lastname: Mutez
authors.forename: Christer
authors.initials: C
authors.lastname: Nilsson
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Opala
authors.forename: Andreas
authors.initials: A
authors.lastname: Puschmann
authors.forename: Aldo
authors.initials: A
authors.lastname: Quattrone
authors.forename: Manu
authors.initials: M
authors.lastname: Sharma
authors.forename: Peter A
authors.initials: PA
authors.lastname: Silburn
authors.forename: Leonidas
authors.initials: L
authors.lastname: Stefanis
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Uitti
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
authors.forename: Carles
authors.initials: C
authors.lastname: Vilariño-Güell
authors.forename: Karin
authors.initials: K
authors.lastname: Wirdefeldt
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: Georgia
authors.initials: G
authors.lastname: Xiromerisiou
authors.forename: Demetrius M
authors.initials: DM
authors.lastname: Maraganore
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies; D051844:alpha-Synuclein / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; C497604:SNCA protein, human; D051844:alpha-Synuclein; D016875:tau Proteins